Acute lung injury is the rapid disruption of the gas exchange apparatus in response to noxious environmental or endogenous agents. The disease process begins with an explosive inflammatory response in the alveolar wall. In the aftermath of the resultant tissue disruption, extensive granulation of the alveolar airspace ensues, consisting of fibroblasts, capillaries, and their connective tissue products. In patients who die following lung injury, airspace granulation persists. In survivors there is apparent resolution of this granulation tissue followed by orderly reconstitution of the gas exchange apparatus. We hypothesize that this observed regression of granulation tissue results from defined hormonal signals on the alveolar epithelia surface that are capable of inducing the programmed death of fibroblasts and endothelial cells. We have developed preliminary data supporting the hypothesis. To evaluate our hypothesis we have three specific aims: Aim 1. Purify and determine the N-Terminal sequence of the observed bioactive peptide; Aim 2. Examine the potential biological significance of the identified peptide; Aim 3. Compare the mechanism of action of the identified peptide with the well established inducer of endothelial cell apoptosis, TNFalpha. Our long range goal is to identify a physiological signal which is capable of inducing the regression of granulation tissue in patients following acute lung injury, thus providing a potentially new therapeutic avenue.